Yeo Yee Hui, Abdelmalek Manal, Khan Seema, Moylan Cynthia A, Rodriquez Luz, Villanueva Augusto, Yang Ju Dong
Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
Nat Rev Gastroenterol Hepatol. 2025 Mar;22(3):173-190. doi: 10.1038/s41575-024-01021-z. Epub 2024 Dec 9.
Liver cancer is the third leading cause of cancer-related deaths globally, with incident cases expected to rise from 905,700 in 2020 to 1.4 million by 2040. Hepatocellular carcinoma (HCC) accounts for about 80% of all primary liver cancers. Viral hepatitis and chronic excessive alcohol consumption are major risk factors for HCC, but metabolic dysfunction-associated steatotic liver disease is also becoming a dominant cause. The increasing numbers of cases of HCC and changes in risk factors highlight the urgent need for updated and targeted prevention strategies. Preventive interventions encompass strategies to decrease the burden of chronic liver diseases and their progression to HCC. These strategies include nutritional interventions and medications that have shown promise in preclinical models. Although prevailing approaches focus on treating chronic liver disease, leveraging a wider range of interventions represents a promising area to safeguard at-risk populations. In this Review, we explore existing evidence for preventive strategies by highlighting established and potential paths to reducing HCC risk effectively and safely, especially in individuals with chronic liver diseases. We categorize the preventive strategies by the mechanism of action, including anti-inflammatory, antihyperglycaemic, lipid-lowering, nutrition and dietary, antiviral, and antifibrotic pathways. For each category, we discuss the efficacy and safety information derived from mechanistic, translational, observational and clinical trial data, pinpointing knowledge gaps and directions for future research.
肝癌是全球癌症相关死亡的第三大主要原因，预计新发病例将从2020年的905,700例增加到2040年的140万例。肝细胞癌（HCC）约占所有原发性肝癌的80%。病毒性肝炎和长期过量饮酒是HCC的主要危险因素，但代谢功能障碍相关脂肪性肝病也日益成为主要病因。HCC病例数量的增加和危险因素的变化凸显了迫切需要更新的针对性预防策略。预防性干预措施包括减轻慢性肝病负担及其向HCC进展的策略。这些策略包括营养干预措施和在临床前模型中显示出前景的药物。尽管现行方法侧重于治疗慢性肝病，但利用更广泛的干预措施是保护高危人群的一个有前景的领域。在本综述中，我们通过强调有效且安全降低HCC风险的既定和潜在途径，尤其是慢性肝病患者的途径，来探索预防性策略的现有证据。我们根据作用机制对预防策略进行分类，包括抗炎、抗高血糖、降脂、营养与饮食、抗病毒和抗纤维化途径。对于每一类，我们讨论从机制、转化、观察和临床试验数据中得出的疗效和安全性信息，指出知识空白和未来研究方向。
